This project aims to better characterize the neural bases of nicotine craving and emotional responses to smoking cues. Nearly one in four American adults smokes cigarettes and twenty percent of U.S. deaths are caused by diseases linked to smoking. Most of those who start smoking find it difficult to quit. Leading theories of nicotine addiction indicate that emotional and motivational responses to smoking-related cues - such as the sight and smell of cigarettes and other smokers - are important in maintaining nicotine dependence. Brain imaging studies have identified several key regions that are responsive to smoking cues and that are related to reports of craving and affect. To date, research on drug cue reactivity has relied heavily on self-reports of emotions and cravings in response to cues. However, self-reports are limited by participants' willingness and ability to introspect. The current project uses a recently developed indirect behavioral measure of affective responses to drug cues, combined with functional neuro-imaging (fMRI) and traditional self-reports. The indirect measure can be administered during brain imaging to identify regional activity related to performance. The research strategy is to expose smokers and non-smoking participants to smoking-relates images while recording their verbal responses, indirect behavioral responses, and neural responses. A unique aspect of the proposal is integration across several methods to provide converging evidence for neural, behavioral, and subjective components of responses. The goal is to distinguish cortical and sub-cortical activity that is responsive to smoking cues and that is (a) related uniquely to self-reported responses (b) related to the indirect measure but not to self-report responses, (c) related to both or (d) neither. This project takes advantage of the close ties between Duke and UNC instantiated in the Duke-UNC Brain Imaging and Analysis Center (BIAC). The long-term objective is to lay the groundwork for a more extensive project examining reportable and un-reportable neural responses that may uniquely predict nicotine use and cessation versus relapse. The prevalence of nicotine addiction and the widespread health implications of smoking make clear the relevance of these considerations for drug addiction and public health more generally. [unreadable] [unreadable] [unreadable]